Thyroid receptor (TR) regulates many homeostatic processes including basal metabolism, cardiovascular function, body weight, and lipid trafficking. TR modulators are potential therapeutics for obesity and hyperlipidemias but current thyroid analogs have undesirable side effects, particularly cardiac stimulation. To confirm that inhibitors specifically prevent the interaction of TR with the more ..

Thyroid receptor (TR) regulates many homeostatic processes including basal metabolism, cardiovascular function, body weight, and lipid trafficking. TR modulators are potential therapeutics for obesity and hyperlipidemias but current thyroid analogs have undesirable side effects, particularly cardiac stimulation. To confirm that inhibitors specifically prevent the interaction of TR with the steroid receptor coregulator 2 (SRC2), an orthogonal TR-SRC2 interaction assay using Alpha Screen (PerkinElmer) was employed. This assay detects the interaction of the ligand-binding domain of human TR# with a SRC2 peptide, corresponding to a 20 amino acid region of the nuclear receptor interaction domain. Small molecule inhibitors that block the interaction of TR and SRC2 are detected by a decrease in chemiluminescence.

Compound Ranking:Active compounds were assigned a score between 50 and 100 based on compound potency. Inactive compounds were assigned a score of 0 and inconclusive compounds were assigned a score of 25.